Avelumab in combination with Axitinib in patients with advanced Thymic tumours

Phase 1

• Conditions: Histologically confirmed advanced Thymoma B3 or Thymic carcinoma inoperable (Masaoka Stage IIIb or IV).; MedDRA version: 21.1Level: PTClassification code 10055108Term: Thymic cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004048-38-IT
• Lead Sponsor: ISTITUTO EUROPEO DI ONCOLOGIA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

•Histologically confirmed advanced Thymoma B3 or Thymic carcinoma
•Inoperable per local Investigator (Masaoka Stage IIIb or IV).
•Progression after treatment with least one platinum containing chemotherapy regimen
•Measurable disease (RECIST 1.1).
•Age =18 years.
•ECOG PS <2.
•Adequate bone marrow function and organ function:
•Hematopoietic function: total white blood cell count (WBC) = 3000/mm³, absolute neutrophil count (ANC) = = 1.5 × 109/L, platelet count = 100 × 109/L , hemoglobin = 9 g/dL
•Hepatic function: Total bilirubin level = 1.5 × the upper limit of normal (ULN) range and AST and ALT levels = 2.5 × ULN or AST and ALT levels = 5 x ULN (for subjects with documented metastatic disease to the liver).
•Estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula
•Negative serum or urine pregnancy test at screening for women of childbearing potential
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

•Medical illness that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy, including
•Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism (< 6 months prior to enrolment), congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
•Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
•Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive
-Active infection requiring systemic therapy;
-Patients with a history of non-infectious pneumonitis that has required a course of oral or intravenous steroids, or interstitial lung disease or pulmonary fibrosis
-inflammatory bowel disease
•Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for 4 weeks are eligible
•Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent, in particular, any autoimmune syndrome typically associated with thymomas (myasthenia gravis, pure red cell aplasia), including patients with positive anti-AChR and/or anti-MuSK antibodies without clinical signs or symptoms of myasthenia gravis. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
•History of a hematologic or primary solid tumor malignancy, unless in remission for at least 2 years. Patients with pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the cervix are eligible
•Significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications.
•Prior organ transplantation including allogenic stem-cell transplantation.
•Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
•Serious psychiatric or medical conditions that could interfere with treatment.
•Concurrent therapy with approved or investigational anticancer therapeutics.
•Current use of immunosuppressive medication within 7 days prior to start treatment, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
•Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade = 3)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified